Process of manufacture of novel drug delivery system: multilayer tablet composition of thiazolidinedione and biguanides

摘要

A novel patient-convenient, cost effective pharmaceutical composition, comprising of thiazolidinediones and biguanide for controlling hyperglycemia manufactured as multilayer tablet and its process of manufacturing, for immediate release of thiazolidinediones or thiazolidinediones and biguanide and prolonged release of the biguanide only, the tablet comprising of minimum two layers wherein one outer layer comprises of a mixture of excipients and thiazolidinediones or thiazolidinediones and biguanide allowing immediate release of thiazolidinediones or thiazolidinediones and biguanide respectively and the other layer arranged in contact with the immediate release layer which comprises of a novel composition of excipients and a minimum one or more non-biodegradable, inert polymer(s) and the biguanide allowing pH independent prolonged release of the biguanide up to a period of 8-12 hours. The tablets are for once a day dosing. The tablets may optionally be film coated or enrobed by soft gelatin ribbons for additional protection against oxidation, photodegradation, identification, ease of swallowing, taste masking and for aesthetic appeal without altering the dissolution profile.

主权项

1. A process for the manufacture of a bi-layered tablet dosage form for once a day administration, the process comprising:
a) preparing a first granule formulation comprising at least one non-biodegradable inert polymer and a biguanide, or a pharmaceutically acceptable salt thereof, of particle size less than 100 microns to achieve pH independent prolonged in-vitro release of the biguanide or pharmaceutical acceptable salt thereof, wherein the non-biodegradable inert polymer is present in an amount of at least 35% by weight of biguanide in the dosage form; b) preparing a second granule formulation comprising (i) one or more active pharmaceutical ingredients for immediate release selected from thiazolidinediones, sulfonyl ureas, alpha-glucosidase inhibitors, aldose reductase inhibitor inhibitors, statins, squalene synthesis inhibitors, fibrates, angiotensin converting enzymes inhibitor, LDL catabolism enhancers, and pharmaceutically acceptable salts thereof; and (ii) a non-biodegradable inert polymer; c) treating the first and second granule formulations with lubricants; and d) compressing the first and second granule formulations to form the bilayered tablet dosage form; wherein the content of non-biodegradable inert polymer in the second granule formulation is not more than 1.2% by weight of the lubricated second granule formulation, the tablet dosage form contains layers of the first and second granule formulations, and the tablet dosage form provides monophasic prolonged release of the biguanide.